Results 91 to 100 of about 15,125 (218)

A common human MLKL polymorphism confers resistance to negative regulation by phosphorylation

Nature Communications, 2023
Across the globe, 2-3% of humans carry the p.Ser132Pro single nucleotide polymorphism in MLKL, the terminal effector protein of the inflammatory form of programmed cell death, necroptosis. Here we show that this substitution confers a gain in necroptotic
Sarah E. Garnish, Katherine R. Martin, Maria Kauppi, Victoria E. Jackson, Rebecca Ambrose, Vik Ven Eng, Shene Chiou, Yanxiang Meng, Daniel Frank, Emma C. Tovey Crutchfield, Komal M. Patel, Annette V. Jacobsen, Georgia K. Atkin-Smith, Ladina Di Rago, Marcel Doerflinger, Christopher R. Horne, Cathrine Hall, Samuel N. Young, Matthew Cook, Vicki Athanasopoulos, Carola G. Vinuesa, Kate E. Lawlor, Ian P. Wicks, Gregor Ebert, Ashley P. Ng, Charlotte A. Slade, Jaclyn S. Pearson, André L. Samson, John Silke, James M. Murphy, Joanne M. Hildebrand   +30 more
doaj   +1 more source

Targeting necroptosis protects against astrocyte death and hippocampal sclerosis in experimental temporal lobe epilepsy

The Journal of Physiology, EarlyView.
Abstract figure legend Experimentally induced status epilepticus induces microglial TNFα release, which binds to astrocytic TNFR1 and triggers activation of RIPK1/RIPK3/MLKL signalling, initiating necroptotic astrocytic death that contributes to the development of hippocampal sclerosis. Created with Biorender.com.
Zhou Wu, Lukas Henning, Christian Steinhäuser, Peter Bedner   +3 more
wiley   +1 more source

A Plug Release Mechanism for Membrane Permeation by MLKL [PDF]

Structure, 2014
MLKL is crucial for necroptosis, permeabilizing membranes through its N-terminal region upon phosphorylation of its kinase-like domain by RIP3. However, the mechanism underlying membrane permeabilization is unknown. The solution structure of the MLKL N-terminal region determined by nuclear magnetic resonance spectroscopy reveals a four-helix bundle ...
Su, Lijing, Quade, Bradley, Wang, Huayi, Sun, Liming, Wang, Xiaodong, Rizo, Josep   +5 more
openaire   +2 more sources

The mitochondrial‐targeted antioxidant SkQ1 prevents skeletal muscle mitochondrial‐apoptotic but not necroptotic signalling during ovarian cancer

The Journal of Physiology, EarlyView.
Abstract figure legend An evaluation of the degree to which mitochondrial hydrogen peroxide emission (mH2O2)‐mediated apoptotic and necroptotic signalling contributes to skeletal muscle atrophy in an orthotopic epithelial ovarian cancer (EOC) model. To determine whether attenuating mH2O2 could prevent regulated cell death signalling and mitigate muscle
Shahrzad Khajehzadehshoushtar, Luca J. Delfinis, Fasih A. Rahman, Madison C. Garibotti, Shivam Gandhi, Aditya N. Brahmbhatt, Brooke A. Morris, Bianca Garlisi, Sylvia Lauks, Caroline Aitken, Leslie Ogilvie, Zhu‐Xu Zhang, Jeremy A. Simpson, Joe Quadrilatero, Jim Petrik, Christopher G. R. Perry   +15 more
wiley   +1 more source

Mixed Lineage Kinase Domain‐Like Protein (MLKL): From Mechanisms to Therapeutic Opportunities

Advanced Science
Lytic forms of regulated cell death (RCD) rely on the activation and recruitment of executioner proteins. The mixed lineage kinase domain‐like protein (MLKL) acts as the executioner in the necroptosis pathway, transitioning from an inactive to active ...
Lijuan Xu, Chunlin Zhuang
doaj   +1 more source

Clnk plays a role in TNF-alpha-induced cell death in murine fibrosarcoma cell line L929 [PDF]

, 2015
Clnk/MIST在一系列细胞因子依赖的造血细胞系中表达，同时也在一些细胞因子非依赖的肥大细胞系中表达，并且能够与PLC，Grb2，ADAP和HPK-1等蛋白相互作用。 作为Blnk/SLP-76接头分子蛋白家族的第三个成员，Clnk参与免疫受体信号通路的正向调控。但是，在Clnk基因敲除鼠中，Clnk对T细胞，NK细胞和肥大细胞的正常分化和发育并不是必须的。 本论文发现了Clnk在免疫信号通路之外的一些功能。我们发现Clnk在一系列细胞因子非依赖的非造血细胞系中表达，比如L929 ...
徐盟
core   +1 more source

Beyond nocardioform: Transcriptionally active microbes and host responses in equine mucoid placentitis

Equine Veterinary Journal, Volume 58, Issue 2, Page 601-618, March 2026.
Abstract Background Nocardioform placentitis (NP) is an understudied form of equine placentitis historically attributed to nocardioform bacteria, yet it remains uncertain whether these organisms are the sole pathogens involved. Objectives To elucidate the pathophysiology of NP and the host–pathogen interaction. Study Design In vivo clinical multi‐omics
Machteld van Heule, Margo Verstraete, Jamie Kaj Norris, Kinga Barbara Graniczkowsa, Kirsten E. Scoggin, Hossam El‐Sheikh Ali, Barry A. Ball, Ward De Spiegelaere, Peter Daels, Bart C. Weimer, Pouya Dini   +10 more
wiley   +1 more source

Phosphorylation-dependent pseudokinase domain dimerization drives full-length MLKL oligomerization

Nature Communications, 2023
The necroptosis pathway is a lytic, pro-inflammatory mode of cell death that is widely implicated in human disease, including renal, pulmonary, gut and skin inflammatory pathologies.
Yanxiang Meng, Sarah E. Garnish, Katherine A. Davies, Katrina A. Black, Andrew P. Leis, Christopher R. Horne, Joanne M. Hildebrand, Hanadi Hoblos, Cheree Fitzgibbon, Samuel N. Young, Toby Dite, Laura F. Dagley, Aarya Venkat, Natarajan Kannan, Akiko Koide, Shohei Koide, Alisa Glukhova, Peter E. Czabotar, James M. Murphy   +18 more
doaj   +1 more source

Procyanidin Capsules Combat ALF by Restoring Mitochondrial Homeostasis and Inhibiting Necroptosis via the PGAM5/DRP1/PINK1 Pathway

Advanced Science, Volume 13, Issue 7, 3 February 2026.
A biomimetic self‐assembly strategy, Procyanidin Capsules (PC‐Ca), has been developed, which has great stability, bioavailability, and liver‐targeting efficacy and modulates the KEAP1‐NRF2 axis to inhibit ROS formation and necroptosis, regulate mitochondrial homeostasis through the PGAM5/DRP1/PINK1 signaling pathway in thioacetamide (TAA)‐induced ALF ...
Qing Shi, Minmin Wu, Jinwei Zhong, Chao Chen, Zhuang Huang, Jingxuan Peng, Dong Yang, Xingjie Zan, Zhengfei Wang   +8 more
wiley   +1 more source

MLKL is involved in the regulation of skin wound healing and interplay between macrophages and myofibroblasts in mice

Scientific Reports
Mixed lineage kinase domain-like protein (MLKL), a critical necroptosis effector, is strongly linked to inflammation, a key component of skin wound healing. However, its precise role in the wound healing process remains inadequately characterized.
Jiamin Zhao, Shuangyi Zhang, Yunjie Bai, Zhiguo Gong, Wenhui Bao, Zhuoya Yu, Bo Liu, Wei Mao, Surong Hasi   +8 more
doaj   +1 more source